Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells.

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells (HUCMSCs). Utilizing dual-nozzle and cell electrospinning techniques, the system encapsulates L-ascorbic acid-2-phosphate magnesium (ASP), ß-glycerophosphate sodium and dexamethasone (DEX) within the fibers, ensuring sustained osteogenic differentiation. The scaffold's morphology, characterization, hydrophilicity, mechanical properties and cellular behavior were examined. Immediate subcutaneous implantation in rabbits was conducted to observe its ectopic osteogenic induction effect. Successfully fabricated P34HB ultrafine fiber slow-release system. Characterization confirmed the uniform distribution of HUCMSCs and inducing components within the scaffold, with no chemical reactions affecting the active components. In vitro tests showcased a prolonged release of DEX and ASP, while biocompatibility assays highlighted the scaffold's suitability for cellular growth. Alizarin Red, type I collagen, and osteopontin (OPN) staining verified the scaffold's potent osteogenic induction effect on HUCMSCs. Notably, immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks. These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction, marking a promising advancement in bone tissue engineering.

Intraoperative radiographic analysis and adjustment of the optimal position of plate in high tibial osteotomy.

BACKGROUND: When high tibial osteotomy is performed for genu varus deformity, it is not easy to determine the accurate placement of the plate. PURPOSE: To determine a simple way to assess the position of the plate, to provide more effective mechanical support and to reduce the risk of implant rupture and vascular injury. MATERIAL AND METHODS: Two human anatomical marks, the patellar ligament and semimembranosus, were connected and divided into four parts to identify points Ⅰ, Ⅱ, and Ⅲ. These points determined the areas for Tomofix placement: anterior, anterolateral, and lateral. Simulated internal fixation placed hole B of Tomofix at points Ⅰ (anterior), Ⅱ (anterolateral), and Ⅲ (lateral). We analyzed the pointing direction of the locking screws in Tomofix holes on MRI to assess potential injury risk to the popliteal neurovascular bundle. RESULTS: In the X-ray: holes B and C appeared as the plate in the anterior, only hole C appeared as the plate in the anterolateral, and none of the holes appeared as the plate in the lateral. In the general view of the sawbones, the screw pointed towards the popliteal neurovascular bundle when the plate was in the anterior. CONCLUSION: If a small number of holes on the plate is visible under fluoroscopy, then several lateral positions of the plate can be obtained; the direction of the screw tunnel tends to deviate from the popliteal neurovascular bundle with the posterior position of the plate.

Biomechanical analysis of different fixation methods for Rorabeck II supracondylar femoral fractures after total knee arthroplasty.

BACKGROUND: Locking plate (LP) and retrograde intramedullary nailing (RIMN) are widely used to fix Rorabeck II supracondylar femoral fractures after total knee arthroplasty (TKA). The biomechanical properties of the implant used for treatment influence its longevity. Therefore, we aimed to evaluate the biomechanical stability of different fixations using finite element analysis. METHODS: Seven finite element models (FEMs) were established, including LP groups (short LP, long LP, and double LP), RIMN groups (short RIMN and long RIMN), and mixed groups (long LP with short RIMN and long LP with long RIMN). The stress of the implants around the fracture area was calculated to evaluate the biomechanical stability under loads. RESULTS: Stress was mainly distributed around the fracture area in all models. The stress-shielding phenomenon was most evident in the short LP. The trend in maximum equivalent stress values of implants around the fracture area for the seven internal fixations was: short LP (324.63 MPa) > short RIMN (306.37 MPa) > long LP (275.06 MPa) > long RIMN (262.74 MPa) > double LP (203.19 MPa) > long LP with short RIMN (124.42 MPa) > long LP with long RIMN (112.41 MPa). We found that the double LP can better disperse the stress than a single LP, and a long LP with long RIMN can prevent stress concentration and make the stress distribution more uniform. CONCLUSION: From the perspective of biomechanics, long LP with long RIMN can stabilize fractures and avoid stress concentration in Rorabeck II supracondylar femoral fractures after TKA.

In situ cell electrospun using a portable handheld electrospinning apparatus for the repair of wound healing in rats.

Slow or non-healing wounds caused by full-thickness skin wounds of various origins have become a difficult challenge in clinical wound treatment. In particular, large full-thickness skin wounds often lead to serious chronic skin wounds that do not heal. Electrospinning technology and stem cell treatment for wound repair have attracted much attention due to its unique advantages. In the current study， we electrospun polyvinyl alcohol (PVA) and bone marrow-derived stem cells (BMSCs) by a handheld electrospinning device, the distribution and interaction of cells and fibres were determined by light and electron microscopy and the cell viability and proliferation were determined by live/dead cell staining. The tissues were analysed by histology with Haematoxylin and Eosin (H&E) and Masson staining and immunohistochemical staining. We found that the fibres were distributed uniformly and BMSCs were distributed between the fibres. Cytotoxicity and cell proliferation tests proved its good biocompatibility. Histological staining shows it can accelerate wound healing and appendages regeneration by promoting granulation tissue repair. The instant PVA/stem cell fibres prepared by a handheld electrospinning device strongly promote the repair of full-thickness skin wounds in rats. The proposed electrospinning technology is expected to have great potential in household, outdoor and battlefield first aid.

Agarose composite hydrogel and PVA sacrificial materials for bioprinting large-scale, personalized face-like with nutrient networks.

Large, deep, complex, and severe tissue defects and deformities of the face are the problems encountered in clinical practice. Autologous tissue reconstruction or allograft face transplantation has been adopted but has problems such as blood supply difficulties, collateral damage, immune rejection, and ethical disputes. 3D bioprinting enables personalized tissue regeneration. However, simple hydrogels are prone to collapse during printing, are limited in size, and have poor shape and structure. The present study used three polysaccharide hydrogel composites of nanocellulose, agarose, and sodium alginate with seeded cells as bioinks and polyvinyl alcohol (PVA) as sacrificial material to construct the structures that did not collapse (characteristic parts, such as lips and nose). The nutrient network gradually formed a blood vessel-like structure. The hydrogels prepared using these three polysaccharides have great potential in the construction of personalized, complex, and vascularized tissue-engineered anatomical faces and provide a new strategy for autologous full face reconstruction.

Exendin-4 inhibits atrial arrhythmogenesis in a model of myocardial infarction-induced heart failure via the GLP-1 receptor signaling pathway.

Glucagon-like peptide-1 receptor (GLP-1 receptor) agonists are considered to exert cardioprotective effects in models of acute and chronic heart disease. The present study aimed to investigate the role of exendin-4 (a GLP-1 receptor agonist) in atrial arrhythmogenesis in a model of myocardial infarction (MI)-induced heart failure and to elucidate the mechanisms underlying its effects. For this purpose, male Sprague-Dawley rats underwent sham surgery or left anterior descending artery ligation prior to being treated with saline/exendin-4/exendin-4 plus exendin9-39 (an antagonist of GLP-1 receptor) for 4 weeks. The effects of exendin-4 on atrial electrophysiology, atrial fibrosis and PI3K/AKT signaling were assessed. Rats with MI exhibited depressed left ventricular function, an enlarged left atrium volume, prolonged action potential duration, elevated atrial tachyarrhythmia inducibility, decreased conduction velocity and an increased total activation time, as well as total activation time dispersion and atrial fibrosis. However, these abnormalities were attenuated by treatment with the GLP-1 receptor agonist, exendin-4. Moreover, the expression levels of collagen I, collagen III, transforming growth factor-ß1, phosphorylated PI3K and AKT levels in atrial tissues were upregulated in rats with MI. These changes were also attenuated by exendin-4. It was also found that these exedin-4-mediated attenutations were mitigated by the co-administration of exendin9-39 with exendin-4. Overall, the findings of the present study suggested that exendin-4 decreases susceptibility to atrial arrhythmogenesis, improves conduction properties and exerts antifibrotic effects via the GLP-1 receptor signaling pathway. These findings provide evidence for the potential use of GLP-1R in the treatment of atrial fibrillation.

Exendin-4 Reduces Ventricular Arrhythmia Activity and Calcium Sparks-Mediated Sarcoplasmic Reticulum Ca Leak in Rats with Heart Failure.

The aim of this study was to investigate the effect of exendin-4 (Ex-4) on ventricular arrhythmias and calcium sparks-mediated calcium leak in a myocardial infarction-heart failure model.We studied the influence of exendin-4 on ventricular arrhythmogenesis in a rat myocardial infarction-heart failure model. In vivo arrhythmia studies (electrocardiogram [ECG] telemetry studies), ex vivo arrhythmia studies calcium sparks tests, and analysis of total and phosphorylated ryanodine receptor (RyR) 2 and CaMK-II were carried out in sham group, myocardial infarction (MI) group, MI + Ex-4 and MI + Ex-4 + Exendin9-39 (Ex9-39) groups.ECG telemetry studies showed an antiarrhythmic effect of exendin-4 with reduction of spontaneous ventricular arrhythmias. Exendin-4 abbreviated the APD90, which was longer in the heart failure model, and increase the APD alternans thresholds. Exendin-4 also reduced the susceptibility to burst pacing-induced arrhythmia ex vivo. Subcellular sarcoplasmic reticulum (SR) calcium leak characteristics were tested in four groups of rat cardiomyocytes. Exendin-4 reduced calcium spark mass, spark frequency, and calcium leak, which may be due to reduced S2814-RyR2 and CaMK-II phosphorylation. Co-administration of exendin 9-39 with exendin-4 partly abolished the above-mentioned effect of exendin-4.These findings suggest that exendin-4 exerts an antiarrhythmic effect through decreasing SR calcium leak in spontaneous and burst pacing-induced ventricular arrhythmias, which may be due to reduced RyR2 phosphorylation and suppressed CaMK-II activity. Exendin-4 may act as a novel antiarrhythmic strategy in heart failure.

Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells.

Homeobox protein Nxk-2.5 (Nkx2.5) is a homeobox transcription factor that promotes chamber-like myocardial gene expression. Data from a previous genome-wide association study suggested that Nkx2.5 may be associated with the genetic variation that underlies atrial fibrillation (AF). Nkx2.5 loss of function has been demonstrated to be associated with an increasing susceptibility of familial AF. Therefore, the aim of the present study was to investigate the effect of Nkx2.5 loss of function on electrophysiological substrates in HL-1 cells. To the best of our knowledge, the results demonstrated for the first time that Nkx2.5 expression was significantly decreased in a rat model exhibiting AF. The effect of silencing Nkx2.5 was assessed following transfection with adenoviral vectors with specific NKX2.5-shRNA. The effect of Nkx2.5 silencing on potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), gap junction alpha-5 protein (Cx40), calcium handling proteins and protein Wnt-11 (Wnt11) expression levels was also assessed in HL-1 cells. The results revealed that Nkx2.5 silencing increased HCN4 expression, decreased Cx40 expression and disrupted the expression of calcium handling proteins. Additionally, Wnt11 signal protein expression was decreased following Nkx2.5 silencing. The results of the present study demonstrated that Nkx2.5 served as a transcriptional regulator of the electrophysiological substrates associated with AF.

Development and Application of a No-Clog Surgical Suction Tip Using 3D Printing Technology.

BACKGROUND Clogging of the suction tip frequently occurs during orthopedic surgery. We developed a novel anti-clog suction tip using 3D printing technology to improve orthopedic surgery efficiency. MATERIAL AND METHODS We studied the root causes of obstructions in suction tips currently employed in orthopedic surgery during actual surgical cases. CAD software and 3D printer was used to design, modify, and print the novel suction tip. The frequency of clogging, the frequency of replacement of the suction tip, the time lost in replacing suction tips or connecting tubes, surgical duration, intraoperative surgical blood loss, and the satisfaction scores for the suction tips as rated by the surgeons were compared between the novel suction tip and the conventional suction tip. Comparisons were made first in laboratory experiments using a simulant liquid and then during total hip replacement surgeries. RESULTS In the simulant liquid experiments, the novel suction tips showed significantly reduced frequency of complete clogging and decreased time spent removing all fluid in comparison to the conventional suction tips (p<0.05). In the clinical trials, the novel suction tips exhibited significantly reduced frequency of complete clogging, shorter surgical duration, and reduced intraoperative surgical blood loss compared to the conventional suction tips (p<0.05). Surgeon satisfaction scores were higher for the novel tips than for the conventional tips (p<0.05). CONCLUSIONS Our surgeon-designed and -produced surgical suction tip utilizing 3D desktop printing technology was highly effective in resolving the problem of clogged suction tips during orthopedic surgery and yielded high surgeon satisfaction.